This proposal aims to clarify and understand the physiological nature of the effects of hormones on brain dopaminergic neurotransmission. Progesterone (P), prolactin (PRL) and photoperiod can markedly modify the activity of the rat nigrostriatal dopamine (NS-DA) system. P exerts a biphasic action on this system, facilitation followed by inhibition; PRL stimulates the release of DA from male but not from female CS and is capable to evoke grooming and yawning behavior when infused locally within the CS of male rats; and photoperiodic cues appear to exert robust bidirectional influences on the NS-DA system since in vitro CS dopamine activity increases in the morning and decreases in the afternoon in diestrus 1 and 2 rats and these diurnal variations are blocked during the transition from proestrus-estrus. To clarify and better understand the physiological nature of the effect of photoperiod, hormones and their interactions upon the function of the NS-DA system we have chosen three strategies. Strategy I - Push-Pull Cannula (PPC) on-line with High Performance Liquid Chromatography with Electrochemical Detection (HPLC-EC) to estimate the simultaneous in vivo output of a series of neuroactive substances during a 24h period from discrete brain areas of conscious, freely behaving animals. Strategy II - in vitro superfusion to measure the temporal and magnitude of the neuroactive substances released from isolated brain fragments under rigorously controllable experimental conditions. Strategy III - biochemical determinations of cAMP levels and adenylate cyclase activity in specific brain areas. Using these three strategies we will delineate the physiological nature and gain an insight in mechanisms by which P, PRL and photoperiod affect neurotransmission of the NS-DA neuronal system. The significance of these studies reside in the fact that little is known of the action of hormones upon the CS, an extra-hypothalamic structure which bridges neuroendocrine mechanisms with motor, sensory and cognitive functions of the NS-DA system. The combination of hormone and drug infusions locally into the CS of fully awake rats with simultaneous measurements of neurochemical and behavioral responses add a new dimension to the analyses of the NS-DA system. Our studies using in vivo and in vitro methodologies will help to gain a better insight on the biology of hormonal action upon the CS and to aid the understanding of the role of hormones in extrapyramidal motor disfunctions.